Dey, Goutam ; Bharti, Rashmi ; Das, Anjan Kumar ; Sen, Ramkrishna ; Mandal, Mahitosh (2017) Resensitization of Akt induced docetaxel resistance in breast cancer by ‘Iturin A’ a lipopeptide molecule from marine bacteria bacillus megaterium Scientific Reports, 7 (1). Article ID 17324-11 pages. ISSN 2045-2322
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Official URL: https://www.nature.com/articles/s41598-017-17652-z
Related URL: http://dx.doi.org/10.1038/s41598-017-17652-z
Abstract
Development of the resistance is the major problem in cancer therapy. Docetaxel is a taxol alkaloid that is frequently used in metastatic breast cancer. However, resistance often limits the usefulness of this drug in many breast cancer patients. Manipulation of resistant cells to re-sensitize to the therapeutic effect of docetaxel is current strategy to overcome this problem. Here, we have introduced ‘Iturin A’ as a potent chemosensitizer in docetaxel resistant breast cancer cells. Combination of Iturin A and docetaxel treatment significantly hampered the proliferation of docetaxel resistant MDA-MB-231 and MDA-MB-468 breast cancer cells. Cell cycle analysis also showed massive amount of apoptotic population (Sub G0G1) in combination therapy. A number of apoptotic and anti-apoptotic proteins were significantly altered in dual drug treated groups. Caspase 3 dependent cell death was observed in dual treatment. Molecular mechanism study showed that over-expression of Akt and its downstream signaling pathway was associated with docetaxel resistance. Iturin A significantly reduced Akt signaling pathway in resistant cells. This mechanistic action might be the reason behind the chemo-sensitization effect of Iturin A in docetaxel resistant breast cancer cells. In conclusion, Iturin A resensitized the resistant breast cancer cells to docetaxel therapy by inhibiting Akt activity.
Item Type: | Article |
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Source: | Copyright of this article belongs to Nature Publishing Group. |
ID Code: | 113335 |
Deposited On: | 09 May 2018 08:24 |
Last Modified: | 09 May 2018 08:24 |
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